Brainstem dysfunction


Senior Member
Hyperintense sensorimotor T1 spin echo MRI is associated with brainstem abnormality in chronic fatigue syndrome
Author links open overlay panelLeighton R.BarndenaZack Y.ShanaDonald R.StainesaSonyaMarshall-GradisnikaKevinFineganbTimothyIrelandbSandeepBhutab
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We recruited 43 Chronic Fatigue Syndrome (CFS) subjects who met Fukuda criteria and 27 healthy controls and performed 3T MRI T1 and T2 weighted spin-echo (T1wSE and T2wSE) scans. T1wSE signal follows T1 relaxation rate (1/T1 relaxation time) and responds to myelin and iron (ferritin) concentrations. We performed MRI signal level group comparisons with SPM12. Spatial normalization after segmentation was performed using T2wSE scans and applied to the coregistered T1wSE scans. After global signal-level normalization of individual scans, the T1wSE group comparison detected decreased signal-levels in CFS in a brainstem region (cluster-based inference controlled for family wise error rate, PFWE= 0.002), and increased signal-levels in large bilateral clusters in sensorimotor cortex white matter (cluster PFWE < 0.0001). Moreover, the brainstem T1wSE values were negatively correlated with the sensorimotor values for both CFS (R2 = 0.31, P = 0.00007) and healthy controls (R2 = 0.34, P = 0.0009), and the regressions were co-linear. This relationship, previously unreported in either healthy controls or CFS, in view of known thalamic projection-fibre plasticity, suggests brainstem conduction deficits in CFS may stimulate the upregulation of myelin in the sensorimotor cortex to maintain brainstem – sensorimotor connectivity. VBM did not find group differences in regional grey matter or white matter volumes. We argued that increased T1wSE observed in sensorimotor WM in CFS indicates increased myelination which is a regulatory response to deficits in the brainstem although the causality cannot be tested in this study. Altered brainstem myelin may have broad consequences for cerebral function and should be a focus of future research.

(c) Sciencedirect


Senior Member
Me neither. :confused: I'm wondering if they're measuring some effect of simply being ill and not doing as much physical activity as healthy people. Have ME, spend more time in bed, and the muscles and their neural connections change a bit. If you measure really small changes in something, it's easy to find correlations that are meaningless.

Maybe this really is a critical discovery, and it will lead to an understanding of what is causing ME, but the abstract doesn't fill me with hope.
Alabama USA
I am just thinking that because many ME patients begin in the teen years with a high fever and viral infections, then get worse with neck trauma or continued fevers that is the link here.

I noticed this process starts in the first year of life and continues to grow well into the latter teen years.
I had high fevers as a child from tonsillitis and it took years for me to get better. I had mono as a teen and chicken pox at 22 and never rested fully. Then a long almost complete remission, then some bad car wrecks and more high fevers with viral infections. Plus a huge personal crisis with major stressors, many horrible things in a row for about 3 years.

finally BAM, fever of 104 F and housebound and disabled. I have always felt that all those high fevers especially with a family who made me go to school when I was horribly ill. Has wrecked my body and brain. Inflammation! Brain and spinal cord trauma!

I am not educated in to science or medicine, and had to google many things in the article and relate all of it to my personal history, that is just my take on it and I could be way off base.

Research 1st

Severe ME, POTS & MCAS.
It suggests the brains scanned have some evidence of being under attack by the immune system. This makes sense in patients with existing evidence of chronic immune activation with neuro disabilities, so we're onto a good first step.

Causes could range from from past or present infection or by error in an autoimmune response and likely numerous other reasons such as oxidative stress.

Basically the brain is trying to protect itself by producing more Myelin. In simple terms, reverse MS, or maybe variant MS? A form where X occurs instead of Y. X can't be Y, but the differing outcome (CFS vs MS) may share a common element, such as exposure to a shared pathogen at onset, e.g. EBV.

There's been MRS (MRI Spectroscopy) scans done in CFS before that imply the CFS brain is under attack (inflammation). In the MRS scans I noticed the NAA was elevated. That's a peculiar finding as in neuro disease, such as MS or Lyme, you find NAA is lower as neurons become damaged, so the signal intensity (peak) reduces. Yet in CFS, this can be increased. The confusing issue here, is CFS patients scanned are never in the same stage of their illness. Mild, moderate, severe. Sick 5 years, sick 25 years Also patients with psych disorders are removed from CFS studies, yet ironically, psych disorders are more prevalent in patients with hard-core Neuro disease than mild, as inflammation affects our minds and behaviour - see Parkinson's psychosis for example.

So as this study is only Fukuda criteria (doesn't mean much) it would have more relevance if the CFS patients in this study had additional supportive evidence of neuro CFS abnormalities, such as additional scanning techniques that correlate with other organic abnormalities found in CFS.

Armed with this evidence, (as Fukuda CFS is so vague a diagnosis), you'd have more idea that these findings link to organic CFS states, rather than simply 'Chronic Fatigue' alone.

So for me, I'd like to see them have additional scans like the MRS mentioned to look for changes in: Choline, Lactate, NAA and Tryptophan and also the old classics such as SPECT/PET for blood flow, FDG-PET for glucose and FDG-PET for neuron inflammation using the latest tracers that the Japanese researchers are trying out -Nakatomi etc.

On a side note, when people say CFS features brain inflammation, they mean the neurons are affected not the swelling of brain tissue. If it was tissue you'd have far more extreme symptoms and it would be visible on standard imaging scans.

This complex,novel or 'low grade' inflammation we suffer from is why psychiatrists laugh at the concept CFS is an inflammatory brain disease but they then keep quiet the neuropsych symptoms of CFS, are explained by microglial inflammation - which is still a form of inflammation, just far less dramatic.

Logic would say, that fatal outcome extreme ME cases, lack this 'protection' seen in your average CFS patients brains, on scanning. So for reasons we don't know but need to discover, why is there primary progressive MS and why is their progressive ME? Is ME a form of deranged, rare CFS? We don't know as the mega sick patients wither away and aren't studied as they're too sick to be studied. Literally, no data exists on patients with extreme ME, because they exceed CFS criteria anyway and are never part of any study due to acquiring other secondary conditions with known causes of 'Chronic Fatigue'. For example; having Thyroid issues, Diabetes, Asthma or Kidney disease gets you barred from a CFS study yet these precise ailments are found in long term more severe patients all the time! This is how we've all been ignored for decades, through inappropriate diagnostic and research criteria misrepresenting who we are, to the wider medical profession and politicians. Without political drive, the huge money we need for research, is never granted.

These sorts of specialist imaging studies in CFS can potentially help sort out everything from core groups to sub groups. They're worth it, but rarely followed up on due to serial lack of funds. What was interesting in this study as well, is they haven't found what they did, in healthy people. So until proven otherwise, that's one in the eye for the CFS is Somatization Disorder theorists, the people who siphon off precious research money into the wrong area of medicine.
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